{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:57:23Z","timestamp":1785585443735,"version":"3.56.0"},"reference-count":23,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX111\u201010905NI"],"award-info":[{"award-number":["NHRI\u2010EX111\u201010905NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI\u2010EX112\u201011229NI"],"award-info":[{"award-number":["NHRI\u2010EX112\u201011229NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was undertaken to evaluate the safety, feasibility, and efficacy of low\u2010intensity focused ultrasound (LIFU) as a noninvasive neuromodulation technique in patients with drug\u2010resistant epilepsy (DRE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this pilot, single\u2010blind, randomized sham\u2010controlled crossover trial, 12 patients with DRE underwent both LIFU and sham stimulation in a randomized sequence, targeting the seizure onset zone (SOZ), each followed by a 4\u2010week observation period. Seizure frequency was analyzed as proportional change from baseline using linear mixed\u2010effects models. An open\u2010label extension phase evaluated longitudinal seizure outcomes following LIFU. Safety assessments included neurological examinations, magnetic resonance imaging (MRI), and neuropsychological and quality of life (QOL) measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During the crossover phase, LIFU did not significantly reduce seizure frequency compared with sham (estimate\u2009=\u2009.49, 95% confidence interval [CI] = \u2212.04 to 1.01,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.068). No period or sequence effects were observed. Conversely, during the open\u2010label extension phase, seizure frequency demonstrated a significant longitudinal reduction following LIFU (\u03b2\u2009=\u2009\u221214.0 percentage points per month, 95% CI = \u221222.2 to \u22125.8,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.001). Post\u2010LIFU MRI showed no structural lesions. No significant changes were observed in anxiety, depression, or QOL scores. There were only transient mild\u2010to\u2010moderate adverse events reported, without serious complications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>LIFU neuromodulation targeting the SOZ is safe and well tolerated. Although the primary crossover analysis did not demonstrate a statistically significant antiseizure effect, delayed seizure reduction during the extended follow\u2010up suggests potential sustained neuromodulatory effects. Larger parallel\u2010group trials with longer observation periods are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70404","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T11:09:43Z","timestamp":1785582583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Low\u2010intensity focused ultrasound neuromodulation for drug\u2010resistant epilepsy: A randomized, sham\u2010controlled crossover trial"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0606-377X","authenticated-orcid":false,"given":"Chien\u2010Chen","family":"Chou","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-2739","authenticated-orcid":false,"given":"Yen\u2010Cheng","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5226-4994","authenticated-orcid":false,"given":"Yi\u2010Hsiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-8352","authenticated-orcid":false,"given":"Po\u2010Tso","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5831-6620","authenticated-orcid":false,"given":"Chun\u2010Fu","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Neurosurgery, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8788-982X","authenticated-orcid":false,"given":"Po\u2010Chun","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3512-7215","authenticated-orcid":false,"given":"Hao\u2010Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Electrical Engineering National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4691-2913","authenticated-orcid":false,"given":"Cheng\u2010Chia","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Department of Neurosurgery, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8183-1863","authenticated-orcid":false,"given":"Hsiang\u2010Yu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurological Institute Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming Chiao Tung University  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming Chiao Tung University  Taipei 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